CIGB-552: A new penetrating peptide with antitumor action mediated by the increased levels of the COMMD1 protein in cancer cell lines

M Guerra-Vallespi; JR Fernández-Massó; B Oliva-Argüelles; O Reyes-Acosta; HE Garay-Pérez; L Delgado-Roche; A Cabrales-Rico; G Pimentel; J Garza; T Basaco; I Sánchez; C Calderón; JC Rodríguez; Y Tejeda-Gómez; O Mendoza-Fuentes; Y Soria; I Guillen-Pérez; D Palenzuela-Gardon; D Vázquez-Blomquist; A Musacchio-Lasa; S Astrada; M Bollati-Fogolín; LI Novoa-Perez; Y Gómez-Rodríguez; M Rivera-Markelova; Fichtner I

2015, Number 3

Biotecnol Apl 2015; 32 (3)

CIGB-552: A new penetrating peptide with antitumor action mediated by the increased levels of the COMMD1 protein in cancer cell lines

Guerra-Vallespi M, Fernández-Massó JR, Oliva-Argüelles B, Reyes-Acosta O, Garay-Pérez HE, Delgado-Roche L, Cabrales-Rico A, Pimentel G, Garza J, Basaco T, Sánchez I, Calderón C, Rodríguez JC, Tejeda-Gómez Y, Mendoza-Fuentes O, Soria Y, Guillen-Pérez I, Palenzuela-Gardon D, Vázquez-Blomquist D, Musacchio-Lasa A, Astrada S, Bollati-Fogolín M, Novoa-Perez LI, Gómez-Rodríguez Y, Rivera-Markelova M, Fichtner I

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ABSTRACT

A second-generation peptide CIGB-552, with cell-penetrating capacity, was developed by the modification of the primary structure of the L-2 peptide. The molecular mechanism underlying its cytotoxic activity remains partially unknown. In this study, it was shown that CIGB-552 binds and increases the levels of COMMD1, a protein involved in copper homeostasis, sodium transport, and the NF-kB signaling pathway. We found that CIGB-552 induces ubiquitination of RelA and inhibits the antiapoptotic activity regulated by NF-kB, whereas the knockdown of COMMD1 blocks this effect. We also found that CIGB-552 increases the levels of reactive oxygen species (ROS), decreases the cellular antioxidant capacity and induces the peroxidation of proteins and lipids in tumor cells. Altogether, our results bring new insights into the mechanism of action of CIGB-552. Moreover, its anti-tumoral effect was explored by subcutaneous administration in a therapeutic schedule in syngeneic murine tumors and patient-derived xenograft models. Outstandingly, a significant delay of tumor growth was observed after the administration of CIGB-552 in these experimental settings. Our data reinforce the perspectives of CIGB-552 for targeted therapy against cancer. This research granted the 2014 Award of the Cuban National Academy of Sciences.

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